Further Characterization of Hb Bronovo [α103(G10)His→Leu; HBA2 : c.311A>T] and First Report of the Homozygous State.

Hb Bronovo [alpha 103(G10)His -> Leu, HBA2: c.311A>T] is an alpha-globin variant that interferes with and decreases binding efficiency to alpha hemoglobin (Hb) stabilizing protein (AHSP), a chaperone molecule. The histidine residue at position 103 is integral to the AHSP hydrogen bond formation where disruption results in an increased quantity of cytotoxic free alpha-globin chains, thereby creating a similar pathophysiology as beta-thalassemia (beta-thal). We report a family with Hb Bronovo, including a homozygous proband, which resulted from maternal uniparental disomy (UPD). Although not detected by routine studies in previous reports, the variant protein is visible by intact mass spectrometry (MS).